In the last years, our interpretation of the origin and function of the gonadotropin-releasing hormone (GnRH) neuropeptide superfamily has changed substantially. A main driver for these conceptual changes came from increased investigations into functions and evolutionary lineage of previously identified molluscan GnRH molecules. Emerging evidence suggests not only reproductive, but also diverse biological effects of these molecules and proposes they should most likely be called corazonin (CRZ). Clearly, a more global understanding requires further exploration of species-specific functions and structure of invGnRH/CRZ peptides. Towards this goal, we have identified the full-length cDNA of invGnRH/CRZ peptide in an invertebrate model species, the great pond snail Lymnaea stagnalis, termed ly-GnRH/CRZ, and characterized the transcript and peptide distribution in the central nervous system (CNS) and peripheral organs. Our results are consistent with previous data that molluscan GnRHs are more related to CRZs and serve diverse functions. Hence, our findings support the notion that peptides originally termed molluscan GnRH are multifunctional modulators and that nomenclature change should be taken into consideration.Volumetric muscle loss injury is a common health problem with long-term disabilities. One common treatment is using muscle flaps from donor site, which has limited potentials due to donor site availability and morbidity. Although several stem cell therapies have been evaluated so far, most suffer from limited availability, immune incompatibility, or differentiation potential. Therefore, induced pluripotent stem cells (iPSCs) have a great promise for this purpose due to their unique differentiation, self-renewal, and immunocompatibility. https://www.selleckchem.com/products/opicapone.html Current study was designed to determine therapeutic potential of human iPSCs (hiPSCs) in a mouse model of volumetric muscle loss. Muscles were subjected to excision to generate 30%-40% muscle loss. Next, hiPSCs were differentiated toward skeletal myogenic progenitors and used with fibrin hydrogel to reconstruct the lost muscle. Histologic evaluation of the treated muscles indicated abundant engraftment of donor-derived mature fibers expressing human markers. Donor-derived fibers were also positive for the presence of neuromuscular junction (NMJ), indicating their proper innervation. Evaluation of the engrafted region indicated the presence of donor-derived satellite cells expressing human markers and Pax7. Finally, in situ muscle function analysis demonstrated significant improvement of the muscle contractility in muscles treated with hiPSCs. These results therefore provide key evidence for the therapeutic potential of human iPSCs in volumetric muscle loss injuries.High plasma lactate is emerging as a critical regulator in development and progression of many human malignancies. Small RNAs derived from cleavage of mature tRNAs have been implicated in many cellular stresses, but the detailed mechanisms that respond to lactic acid (LA; acidic lactate) are not well defined. Here, using an Epstein-Barr virus (EBV)-immortalized B lymphoblastic cell line (LCL) as a model, we report that LA induces cleavage of mature tRNA at the anticodon loop, particularly production of three 5'-tRNA halves (5'-HisGUG, 5'-ValAAC, and 5'-GlyGCC), along with increased expression of RNA polymerase III and angiogenin (ANG). Of these, only the 5'-HisGUG half binds to the chromatin regulator argonaute-2 (AGO2) instead of the AGO1 protein for stability. Notably, the levels of ANG and 5'-HisGUG half expression in peripheral blood mononuclear cells from B cell lymphoma patients are tightly correlated with lactate dehydrogenase (LDH; a lactate indicator) in plasma. Silencing production of the 5'-HisGUG half by small interfering RNA or inhibition of ANG significantly reduces colony formation and growth of LA-induced tumor cells in vitro and in vivo using a murine xenograft model. Overall, our findings identify a novel molecular therapeutic target for the diagnosis and treatment of B cell lymphoma.Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease characterized by localized dilation of the abdominal aorta. C1q/tumor necrosis factor (TNF)-related protein-13 (CTRP13) is a secreted adipokine that plays important roles in the cardiovascular system. However, the functional role of CTRP13 in the formation and development of AAA has yet to be explored. In this study, we determined that serum CTRP13 levels were significantly downregulated in blood samples from patients with AAA and in rodent AAA models induced by Angiotensin II (Ang II) in ApoE-/- mice or by CaCl2 in C57BL/6J mice. Using two distinct murine models of AAA, CTRP13 was shown to effectively reduce the incidence and severity of AAA in conjunction with reduced aortic macrophage infiltration, expression of proinflammatory cytokines (interleukin-6 [IL-6], TNF-α, and monocyte chemoattractant protein 1 [MCP-1]), and vascular smooth muscle cell (SMC) apoptosis. Mechanistically, nicotinamide phosphoribosyl-transferase 1 (NAMPT1) was identified as a new target of CTRP13. The decreased in vivo and in vitro expression of NAMPT1 was markedly reversed by CTRP13 supplementation in a ubiquitination-proteasome-dependent manner. NAMPT1 knockdown further blocked the beneficial effects of CTRP13 on vascular inflammation and SMC apoptosis. Overall, our study reveals that CTRP13 management may be an effective treatment for preventing AAA formation.The sentinel lymph node (LN) is the first LN to which lymph fluid flows from tumor tissue. We identified the key parameters of liposomes (LPs) that affect their accumulation in regional (primary) LNs with minimum leakage to its connecting (secondary) LNs by a comprehensive analysis of the LN-to-LN trafficking of LPs with various surface charges and various sizes. We used a lymphatic flow-modified (LFM) mouse that allows for the chronological analysis of inguinal (primary) LN-to-axillary (secondary) LN at the body surface. As a result, the anionic medium-sized LPs (130 nm on average) exhibited the highest accumulation in the primary LNs. A mechanism-based analysis revealed that CD169-positive macrophages in LNs were the dominant cell population that captures anionic LPs. Sentinel LN imaging was also performed by the intratumoral injection of fluorescent medium-sized anionic LPs using a breast cancer orthotopic model. In comparison with the typically used contrast agent indocyanine green, the anionic LPs were detected in sentinel LNs with a high sensitivity.